14-50118294-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_006939.4(SOS2):c.*50T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,469,722 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (35 hom.)
• Consequence: SOS2 NM_006939.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63

Genes affected

SOS2 (HGNC:11188): (SOS Ras/Rho guanine nucleotide exchange factor 2) This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 14-50118294-A-T is Benign according to our data. Variant chr14-50118294-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1202548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00428 (5636/1317370) while in subpopulation SAS AF= 0.0169 (1159/68692). AF 95% confidence interval is 0.0161. There are 35 homozygotes in gnomad4_exome. There are 3027 alleles in male gnomad4_exome subpopulation. Median coverage is 19. This position pass quality control queck.
• BS2: High AC in GnomAd at 503 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOS2	NM_006939.4	c.*50T>A		3_prime_UTR_variant	23/23	ENST00000216373.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOS2	ENST00000216373.10	c.*50T>A		3_prime_UTR_variant	23/23	1	NM_006939.4	P1
SOS2	ENST00000543680.5			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00330 AC: 503 AN: 152234 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00435

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00404 AC: 745 AN: 184588 Hom.: 9 AF XY: 0.00453 AC XY: 450 AN XY: 99416

Gnomad AFR exome AF: 0.000553

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00993

Gnomad EAS exome AF: 0.000128

Gnomad SAS exome AF: 0.0140

Gnomad FIN exome AF: 0.00217

Gnomad NFE exome AF: 0.00404

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00428 AC: 5636 AN: 1317370 Hom.: 35 Cov.: 19 AF XY: 0.00466 AC XY: 3027 AN XY: 649098

Gnomad4 AFR exome AF: 0.000482

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.00791

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.0169

Gnomad4 FIN exome AF: 0.00284

Gnomad4 NFE exome AF: 0.00372

Gnomad4 OTH exome AF: 0.00475

GnomAD4 genome AF: 0.00330 AC: 502 AN: 152352 Hom.: 3 Cov.: 32 AF XY: 0.00346 AC XY: 258 AN XY: 74498

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00435

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00414 Hom.: 1

Bravo AF: 0.00258

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	7.0
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74714090; hg19: chr14-50585012;